From 1958, when this grant was first awarded, until the present, the broad objectives of the project were, identification of gastric and small bowel motor patterns and the mechanisms of their control. Controlling mechanisms, particularly those related to the pacesetter potential, are now sufficiently understood to justify determination of the consequence of their perversion and that is what the researches in this application will attempt. Essentially we aim to alter transit of contents in the stomach, across the gastroduodenal junction and in the small bowel without anatomical alterations in the organs, and to determine the pathophysiological consequences of the misdirection of contents. The investigations are constructed around one concept, now well established, that the pacesetter potential acts as a local controller of gastric and small bowel contractions. We propose to induce duodenal-gastric reflux by creation of an abnormal pacemaker in the distal duodenum and to induce gastric retention by an abnormal pacemaker in the gastric antrum. The effects of chronic pyloric reflux and gastric retention on the gastric mucosa will be tested, particularly looking for barrier breaking. The motor and transit consequences of removal of the frequency gradient of the small bowel will be determined. In all of the studies, chronic electrical pacing of the pacesetter potential will be used. By-products of the researches should be insights into the role of duodenal-gastric reflux and gastric retention in the pathogenesis of gastric ulcer and an estimate of the feasibility and utility of chronic implantation of electrical pacemakers in the stomach and small bowel of patients.